After central nervous system (CNS) injury, a series of stress responses induce astrocytes activation. Reactive astrocytes, which are typically different from astrocytes in normal conditions in altered morphology and gene expression, combine with extracellular matrix (ECM) components to form a glial scar at the lesion site, which walls of the injured region from neighboring healthier tissue. However, as a physical and molecular barrier, glial scar can impede patients' functional recovery in the late period of CNS injury. Thus, inhibiting glial scar formation in the chronic stage after CNS injury may be a promising target to improve outcomes. Since the therapeutic strategies targeting on mediating glial scar formation are regarded as an important part on improving functional recovery after CNS injury, in this review, we focus on the regulating effects of related signaling pathways and other molecules on glial scar, and the process of glial scar formation and the roles that it plays during the acute and chronic stages are also expounded in this article. We hope to get a comprehensive understanding of glial scar during CNS injury based on current researches and to open new perspectives for the therapies to promote functional recovery after CNS injury.